Molecular neuroimaging in primary progressive aphasia with predominant agraphia

A 62-year-old male presented with progressive isolated writing and spelling difficulties. Neurological, neuropsychological, speech, and language evaluations identified only minimal additional abnormalities. The presenting characteristics did not meet criteria for any particular variant of primary progressive aphasia; his clinical presentation is best described as primary progressive aphasia, with a predominant, almost pure agraphia. Brain MRI showed asymmetric, bilateral parenchymal volume loss, with left hippocampal atrophy. Fluorodeoxyglucose-F18 positron emission tomography showed hypometabolism in the lateral left frontal lobe, including Exner's area. Beta-amyloid and tau-positron emission tomography scans were negative, indicating the etiology was not Alzheimer's disease. The underlying neurodegenerative process is most likely related to TDP-43, although a 4-repeat tauopathy cannot be excluded. Following his clinical evolution, and ultimately identifying the underlying pathology from autopsy, will elucidate the etiology of this interesting clinical presentation.